Probably the most profound group of people affected by systemic fungal infections is those who are in a state of immunosuppression: this can be due to some persistent primary infection (often AIDS, but can be others as well), ongoing chemotherapy or other immunosuppressive treatment.

Furthermore, certain conditions such as malnutrition or old age increase the risk of systemic fungal infections.

Finally, normal antibiotic treatment renders people susceptible to fungal infections, often in the gut. These infections are usually less dangerous than those mentioned above, although they can cause severe consequences especially among the elderly. The mechanism for this is the antibiotic destroying the normal flora in the gastro-intestinal tract, allowing more room for the fungi to grow (which are unaffected by the antibiotic).

In general, systemic fungal infections are rare among healthy individuals, since most of the pathogenic fungi are opportunistic microbes - that is, they do not normally cause disease as long as the function of the host immune system is not compromised.